The mission of the Medications Development Division (MDD) of NIDA is to develop safe and efficacious medical treatments for cocaine and opiate abuse/dependence. These therapeutic agents need to have low abuse liability, diminish the reinforcing effects, curtail the rewarding effects, and decrease the addictive attributes of drugs of abuse. Moreover, there is also a need to moderate and/or eliminate the symptoms associated with withdrawal, and ultimately reduce the use and subsequent relapse to renewed use of these illicit drugs. NIDA intends to minimize the risk of injury to the nervous systems of patients undergoing treatment with new drugs developed by MDD. The primary objective of this research and development contract is to assess the potential of experimental new medical treatment compounds (test compounds) to induce neurotoxicity. Test compounds may interact with illicit drugs and/or a brain altered by such drugs in a manner that will damage the brain. In this contract , rodents will be exposed to test compounds and their brains examined under light microscopic techniques to reveal possible damage to brain tissue caused by the test compound or its interaction with cocaine, methamphetamine or other abused substances. Data generated by this contract will help to determine the safety of candidate medications and will guide decision- making concerning advancement of test compounds in the development process.